Exposure of adult guinea pigs to FIO2 of 85% for 90 hours results in elaboration of increased superoxide anion and hydrogen peroxide from their phagocytizing alveolar macrophages coincident with induction of superoxide dismutase (SOD) until 90 hours and inactivation of catalase and glutathione peroxidase throughout the exposure period. These cells also lose surface receptor activity for complement (C3) but not for IgG (Fc), fail to adhere to artificial surfaces, display diminished rates of pinocytosis and phagocytosis and cannot be capped by fluoresceinated Concanavalin A in response to the microtubule disassembly agent, colchincine. On the other hand, exposure to FIO2 of 50% results in persistent elevation of SOD and a less striking alteration in catalase and glutathione peroxidase. The elevated SOD activity noted at 18 hours is maximal at FIO2 of 50% and is less at higher FIO2, suggesting influx of a less mature population of mononuclear cells from either the blood or marginated pool residing close to the pulmonary endothelium. This project will focus on the biochemical, cytoskeletal, and functional interactions between pulmonary endothelial cells and alveolar macrophages and the alteration in these relationships provoked by varying states of hyperoxia. The oxygenase products of endothelial cells, prostaglandins PGI2 and PGE2, known to raise cAMP levels and reduce surface membrane adherence and aggregation of platelets and decrease motile responses of neutrophils and the potent chemoattractants C5a, C3a, and synthetic formyl-oligopeptides, known to stimulate surface adherence, oxidative responses and motility of phagocytic cells will be employed. Not only will we quantify the release of PGI2, PGE2, from endothelial cells and chemoattractants from lungs after hyperoxia, but their effects on specific membrane-related properties and function will be assessed in alveolar macrophages, endothelial cells, and Type II epithelial cells in vitro. In addition, the effect of a variety of antioxidants and anti-oxygenases will be administered to guinea pigs exposed to hyperoxia in an attempt to abrogate specific cellular derangements ascribed to oxygen toxicity.